Martin Reck, MD, PhD, Head of the Department of Thoracic Oncology at the Lung Clinic Grosshansdorf in Germany, discussed the study at the Presidential Session, calling it “very important work.”
This study shows that, with more sensitive assays, T790M mutations are much more frequent than previously believed. “Even in treatment-naive patients, we see incidence rates up to 38%,” said Dr. Reck. “So it’s clear that the difference is related to the testing method. The deeper you dive, the more you find.”
“The clinical impact of these high-sensitivity results needs to be determined; however, we have very good preclinical data showing that VEGF inhibition may delay the resistance toward EGFR tyrosine kinase inhibitors, related to the T790M mutation,” he added.
“The response rates [to erlotinib plus bevacizumab] are on the upper boundary that we have seen in EGFR-mutated NSCLC,” he noted. “The progression-free survival is nearly 14 months, with an interesting signal of 16 months in patients determined to have T790M-positive tumors.”
“Will the findings change clinical practice? Not directly,” he maintained Dr. Reck. “We have introduced oral compounds to the patients’ convenience, and this convenience would be afflicted by giving bevacizumab [intravenously] every 3 weeks. We also still see some adverse events. And this was a nonrandomized phase II trial.”
Dr. Reck would be interested in seeing how these benefits compare with those of a single-agent third-generation EGFR tyrosine kinase inhibitor, such as AZD9291, and in knowing the molecular patterns of resistance after treatment with erlotinib/bevacizumab.
The phase III RELAY trial could provide validation for combined EGFR and VEGF inhibition. It is comparing erlotinib plus ramucirumab (Cyramza) vs erlotinib alone in patients with EGFR-mutated NSCLC. ■
Disclosure: Dr. Reck has been a member of advisory boards for Hoffmann-La Roche, Lilly, Bristol-Myers Squibb, AstraZeneca, Merck, Boehringer-Ingelheim, Pfizer, and Novartis and has received honoraria from all but Novartis.
